Bacterial population genetics, evolution and epidemiology.

Asexual bacterial populations inevitably consist of an assemblage of distinct clonal lineages. However, bacterial populations are not entirely asexual since recombinational exchanges occur, mobilizing small genome segments among lineages and species. The relative contribution of recombination, as opposed to de novo mutation, in the generation of new bacterial genotypes varies among bacterial populations and, as this contribution increases, the clonality of a given population decreases. In consequence, a spectrum of possible population structures exists, with few bacterial species occupying the extremes of highly clonal and completely non-clonal, most containing both clonal and non-clonal elements. The analysis of collections of bacterial isolates, which accurately represent the natural population, by nucleotide sequence determination of multiple housekeeping loci provides data that can be used both to investigate the population structure of bacterial pathogens and for the molecular characterization of bacterial isolates. Understanding the population structure of a given pathogen is important since it impacts on the questions that can be addressed by, and the methods and samples required for, effective molecular epidemiological studies.     

The interface between genetics and psychology: lessons from developmental dyslexia

Developmental dyslexia runs in families, and twin studies have confirmed that there is a substantial genetic contribution to poor reading. The way in which discoveries in molecular genetics are reported can be misleading, encouraging us to think that there are specific genes that might be used to screen for disorder. However, dyslexia is not a classic Mendelian disorder that is caused by a mutation in a single gene. Rather, like many other common disorders, it appears to involve combined effects of many genes and environmental factors, each of which has a small influence, possibly supplemented by rare variants that have larger effects but apply to only a minority of cases. Furthermore, to see clearer relationships between genotype and phenotype, we may need to move beyond the clinical category of dyslexia to look at underlying cognitive deficits that may be implicated in other neurodevelopmental disorders.     

The relation between multilocus population genetics and social evolution theory

Evolution at multiple gene positions is complicated. Direct selection on one gene disturbs the evolutionary dynamics of associated genes. Recent years have seen the development of a multilocus methodology for modeling evolution at arbitrary numbers of gene positions with arbitrary dominance and epistatic relations, mode of inheritance, genetic linkage, and recombination. We show that the approach is conceptually analogous to social evolutionary methodology, which focuses on selection acting on associated individuals. In doing so, we (1) make explicit the links between the multilocus methodology and the foundations of social evolution theory, namely, Price's theorem and Hamilton's rule; (2) relate the multilocus approach to levels-of-selection and neighbor-modulated-fitness approaches in social evolution; (3) highlight the equivalence between genetical hitchhiking and kin selection; (4) demonstrate that the multilocus methodology allows for social evolutionary analyses involving coevolution of multiple traits and genetical associations between nonrelatives, including individuals of different species; (5) show that this methodology helps solve problems of dynamic sufficiency in social evolution theory; (6) form links between invasion criteria in multilocus systems and Hamilton's rule of kin selection; (7) illustrate the generality and exactness of Hamilton's rule, which has previously been described as an approximate, heuristic result.     

Molecular approaches for a better understanding of the epidemiology and population genetics of Leishmania

Molecular approaches are being used increasingly for epidemiological studies of visceral and cutaneous leishmaniases. Several molecular markers resolving genetic differences between Leishmania parasites at species and strain levels have been developed to address key epidemiological and population genetic questions. The current gold standard, multilocus enzyme typing (MLEE), needs cultured parasites and lacks discriminatory power. PCR assays identifying species directly with clinical samples have proven useful in numerous field studies. Multilocus sequence typing (MLST) is potentially the most powerful phylogenetic approach and will, most probably, replace MLEE in the future. Multilocus microsatellite typing (MLMT) is able to discriminate below the zymodeme level and seems to be the best candidate for becoming the gold standard for distinction of strains. Population genetic studies by MLMT revealed geographical and hierarchic population structure in L. tropica, L. major and the L. donovani complex. The existence of hybrids and gene flow between Leishmania populations suggests that sexual recombination is more frequent than previously thought. However, typing and analytical tools need to be further improved. Accessible databases should be created and sustained for integrating data obtained by different researchers. This would allow for global analyses and help to avoid biases in analyses due to small sample sizes.     

The population genetics of anisogamy

This paper analyses the population genetics of anisogamy controlled by a single locus, in both the haploid and diploid cases. The conclusions of Parker et al. (1972), based on computer calculations, are confirmed analytically. The effects of the existence of two mating types on the evolution of anisogamy are examined. Close linkage between a mating type locus and the gamete size locus may produce non-random associations of alleles, leading to disassortative fusion with respect to gamete size. With loose linkage, there is random association of alleles, but selection favours closer linkage.     

Huntington disease: genetics and epidemiology

Huntington disease (HD) is an autosomal dominant disorder in which the major gene expression occurs in the central nervous system. It is characterized by the appearance of progressive chorea and dementia, usually in adult life. One tragic aspect of the disorder, due to its late age of onset and, until recently, lack of a presymptomatic marker, is that transmission of the disease to offspring invariably occurs before symptoms develop in the parent. Although the onset of symptoms and the rate of progression may vary, the prognosis is one of relentless deterioration. The major pathological features of HD are a primary loss of cells in the caudate nucleus and putamen (striatum) but other regions of the basal ganglia, hypothalamus, and brain stem are also involved. Not only is there neuronal loss but there is also a decrease in the level of a number of neurotransmitters and associated enzymes, together with abnormalities in some receptor sites. Martin [1] described the disease as "genetically programmed cell death in the human central nervous system."     

The systematics and population genetics of Opisthorchis viverrini sensu lato: implications in parasite epidemiology and bile duct cancer

Together with host and environmental factors, the systematics and population genetic variation of Opisthorchis viverrini may contribute to recorded local and regional differences in epidemiology and host morbidity in opisthorchiasis and cholangiocarcinoma (CCA). In this review, we address recent findings that O. viverrini comprises a species complex with varying degrees of population genetic variation which are associated with specific river wetland systems within Thailand as well as the Lao PDR. Having an accurate understanding of systematics is a prerequisite for a meaningful assessment of the population structure of each species within the O. viverrini complex in nature, as well as a better understanding of the magnitude of genetic variation that occurs within different species of hosts in its life cycle. Whether specific genotypes are related to habitat type(s) and/or specific intermediate host species are discussed based on current available data. Most importantly, we focus on whether there is a correlation between incidence of CCA and genotype(s) of O. viverrini. This will provide a solid basis for further comprehensive investigations of the role of genetic variation within each species of O. viverrini sensu lato in human epidemiology and genotype related morbidity as well as co-evolution of parasites with primary and secondary intermediate species of host.     

The development of genetics and population studies

The contribution of genetics and population studies to physical anthropology as reflected in the pages of our Journal is traced since its establishment in 1918. Major trends include the use of more genetic polymorphisms, the search for natural selection and genetic drift, the unraveling of population structure in a wide variety of ecological niches, and the recognition of the role of culture in human biology. Nonhuman primates have also been explored from the viewpoint of population genetic. Emphasis has been increasingly on process rather than classification.     

The population genetics of reinforcing selection

A common outcome of disruptive selection experiments between two differentiated populations which produce disadvantageous hybrids is an increase in homogamy. Experiments reported here result in another outcome when ‘classical’ selection experiments are redesigned. In these modified experiments, frequencies of genotypes in the mating population were not artificially maintained at parity but were instead determined from progeny proportions in the previous generation. In these selection lines another outcome, apart from an increase in homogamy, was demonstrated. Under a high selection coefficient against heterozygotes, elimination of a homozygote and the corresponding fixation of the other was observed. No selection line demonstrated the maintenance of two differentiated populations concurrently with the selection process of heterozygote disadvantage. A high number of generations of selection under this population genetical process is necessary to increase differences between two populations. However, the instability of gene frequencies which results in fixation or elimination of a homozygote is shown to be extremely rapid by comparison. Classical experiments were repeated and after 21 generations of selection there was no increase in divergence. For lower selection coefficients, high levels of introgression are apparent, and hence the genetical distinctness of the two populations decreases over time. This is in addition to the problem of an unstable equilibrium under selection against heterozygotes. Both aspects are important but not previously considered in experimental evidence for speciation models for which their implications are discussed.     

The population genetics of nodule bacteria

The data are reviewed on the population structure and evolutionary dynamics of the nodule bacteria (rhizobia) which are among the most intensively studied microorganisms. High level of the population polymorphism was demonstrated for the rhizobia populations using the enzyme electrophoresis (MLEE profiles). The average value of Nei's coefficient of heterogeneity (H = 1 - sigma pi2 [n/(n - 1)]) were: 0.590 for rhizobia (Rhizobium, Bradyrhizobium), 0.368 for enterobacteria (Escherichia, Salmonella, Shigella) and 0.452 for pathogenic bacteria (Bordetella, Borrelia, Erysipelothrix, Haemophilus, Helicobacter, Listeria, Mycobacterium, Neisseria, Staphylococcus) populations. In spite of being devoid of the effective systems for the gene conjugative transfer, many rhizobia populations possess an essentially panmictic structure. However, the enterobacteria populations in which the gene transfer may be facilitated due to the conjugative F- and R-factors, usually display the clonal population structure. The legume host plant is proved to be a key factor that determines the high levels of polymorphism and of panmixis as well as high evolutionary rates of the symbiotic bacteria populations. The host may ensure: a) an increase in mutation and gene transfer frequencies; b) stimulation of the competitive (selective) processes in both symbiotic and free-living rhizobia populations. A "cyclic" model of the rhizobia microevolution is presented which allows to assess the inputs the interstrain competition for the saprophytic growth and for the host nodulation into evolution of a plant-associated rhizobia population. The nodulation competitiveness in the rhizobia populations is responsible for the frequency-dependent selection of the rare genotypes which may arise in the soil bacterial communities as a result of the transfer of symbiotic (sym) genes from virulent rhizobia strains to either avirulent rhizobia or to the other (saprophytic, phytopathogenic) bacteria. Therefore, the nodulation competitiveness may ensure: a) panmictic structure of the natural rhizobia populations; b) high taxonomic diversity of rhizobia which was apparently caused by a broad sym gene expansion in the soil bacterial communities. The kin selection models are presented which explain evolution of the "altruistic" (essential for the host plant, but not for the bacteria themselves) symbiotic traits (e.g., the ability for symbiotic nitrogen fixation and for differentiation into non-viable bacteroids) in the rhizobia populations. These models are based on preferential multiplication of the nitrogen-fixing clones either in planta (due to an elevated supply of the nitrogen-fixing nodules with photosynthates) or ex planta (due to a release of the rhizopines from the nitrogen-fixing nodules). Speaking generally, interactions with the host plants provide a range of mechanisms increasing a genetic heterogeneity and an evolutionary potential in the associated rhizobia populations.     

The population genetics of multistage carcinogenesis

Despite the many successes of cancer research, we lack the framework necessary to predict the ratio of familial (inherited) to sporadic (non-inherited) cancers. An evolutionary model of multistage carcinogenesis provides this framework by demonstrating that the number of tumour suppressor loci (TSLs) preventing cancer in a given tissue is expected to depend upon the tissue's vulnerability to pre-reproductive somatic mutation. Since this vulnerability increases with tissue size, single gene control of human cancer may be restricted to retinoblastoma, a cancer of the tiny embryonic retina. The model is used to estimate the frequency of mutant alleles causing inherited cancers, based on the population genetics of the mutation-selection balance between new mutations arising and selection that eliminates them. For each specific cancer, this balance is determined by the effectiveness with which pre-reproductive cancer is suppressed in the non-mutant genotype characteristic of that population. Effectiveness depends on an interaction between the number of TSLs suppressing the cancer and factors determining the tissue-wide somatic mutation rate, such as tissue size and number of pre-reproductive cell divisions. The model predicts that the commonest pre-reproductive cancers will have the lowest proportion of familial cases, and that cancers associated with the most TSLs will have the highest post-reproductive incidence but no elevated pre-reproductive risk (a pattern seen in human epithelial cancers).